Utilizing the Hippo pathway as a therapeutic target for combating endocrine-resistant breast cancer

Abstract

Drug resistance is always a great obstacle in any endocrine therapy of breast cancer. Although the combination of endocrine therapy and targeted therapy has been shown to significantly improve prognosis, refractory endocrine resistance is still common. Dysregulation of the Hippo pathway is often related to the occurrence and the development of many tumors. Targeted therapies of this pathway have played important roles in the study of triple negative breast cancer (TNBC). Targeting the Hippo pathway in combination with chemotherapy or other targeted therapies has been shown to significantly improve specific antitumor effects and reduce cancer antidrug resistance. Further exploration has shown that the Hippo pathway is closely related to endocrine resistance, and it plays a “co-correlation point” role in numerous pathways involving endocrine resistance, including related pathways in breast cancer stem cells (BCSCs). Agents and miRNAs targeting the components of the Hippo pathway are expected to significantly enhance the sensitivity of breast cancer cells to endocrine therapy. This review initially explains the possible mechanism of the Hippo pathway in combating endocrine resistance, and it concludes by recommending endocrine therapy in combination with therapies targeting the Hippo pathway in the study of endocrine-resistant breast cancers.

Blockade of a novel MAP4K4-LATS2-SASH1-YAP1 cascade inhibits tumorigenesis and metastasis in luminal breast cancer

“…ER signaling is the main driving force for the growth of ER + breast carcinomas ( 39 ). The noncanonical roles of the components of the Hippo pathway crucially impact ER signaling.…”

“…The noncanonical roles of the components of the Hippo pathway crucially impact ER signaling. YAP1 and TEAD4, coregulators of ERα on enhancers, exhibit augmented binding to ERα upon estrogen stimulation and are required for the induction of target genes of ER signaling ( 39 , 40 ). SASH1 expression was significantly inversely correlated with nuclear ER expression ( Fig.…”

Recent Therapeutic Approaches to Modulate the Hippo Pathway in Oncology and Regenerative Medicine

“…In this context, YAP1-mediated regulation of ferroptosis is starting to be discussed as one of the potential mechanistic links between chemoresistance and high YAP1 activity [49][50][51][52][53]. In addition, an increasing number of studies have shown that the Hippo pathway is closely linked to endocrine therapy resistance in breast and prostate cancer [54,55].…”

RBCK1 is an endogenous inhibitor for triple negative breast cancer via hippo/YAP axis

“…Quite a few studies have revealed the critical function of Hippo signaling in TNBC progression [9][10][11][12]. The normal function of Hippo signaling is important in tissue regeneration, organ size control and cancer prevention [13].…”